Molecular detection of novel WFS1 mutations in patients with Wolfram syndrome by a DHPLC-based assay

Wolfram syndrome (WS) is a recessively inherited mendelian form of diabetes and neurodegeneration also known by the acronym DIDMOAD from the major clinical features, including diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. Affected individuals may also show renal tract abnormali...

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Bibliographic Details
Published in:Human mutation 2003-06, Vol.21 (6), p.622-629
Main Authors: Colosimo, Alessia, Guida, Valentina, Rigoli, Luciana, Di Bella, Chiara, De Luca, Alessandro, Briuglia, Silvana, Stuppia, Liborio, Carmelo Salpietro, Damiano, Dallapiccola, Bruno
Format: Article
Language:English
Subjects:
Adolescent
Adult
Age of Onset
Alleles
Child
Chromatography, High Pressure Liquid
DHPLC
diabetes
DIDMOAD
DNA Mutational Analysis - methods
Exons - genetics
Female
hearing loss
Heterozygote
Humans
Italy
Male
Membrane Proteins - genetics
Molecular Sequence Data
Mutation - genetics
mutation screening
Nucleic Acid Denaturation
Polymorphism, Genetic - genetics
WFS1
Wolfram syndrome
Wolfram Syndrome - genetics
Wolfram Syndrome - physiopathology
wolframin
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Summary:Wolfram syndrome (WS) is a recessively inherited mendelian form of diabetes and neurodegeneration also known by the acronym DIDMOAD from the major clinical features, including diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. Affected individuals may also show renal tract abnormalities as well as multiple neurological and psychiatric symptoms. The causative gene for WS (WFS1) encoding wolframin maps to chromosome 4p16.1 and consists of eight exons, spanning 33.44 Kb of genomic DNA. In this study we report on the mutational analysis of the WFS1 coding region in 19 Italian WS patients and 25 relatives, using a DHPLC‐based protocol. A total of 19 different mutations in WFS1 were found in 18 of 19 patients (95%). All these mutations, except one, are novel, preferentially located in WFS1 exon 8, and include deletions, insertions, duplications, and nonsense and missense changes. In particular, a 16 base‐pair deletion in WFS1 codon 454 was detected in five different unrelated nuclear families, being the most prevalent alteration in this Italian group. Nine neutral changes and polymorphisms were also identified. Overall, this study represents the molecular characterization of the largest cohort of Italian WS patients and carriers studied so far, and increases the number of identified WFS1 allelic variants worldwide. Hum Mutat 21:622–629, 2003. © 2003 Wiley‐Liss, Inc.
ISSN:1059-7794
1098-1004
DOI:10.1002/humu.10215